Involvement of the Up-regulated FoxO1 Expression in Follicular Granulosa Cell Apoptosis Induced by Oxidative Stress

Shen, Ming; Lin, Fei; Zhang, Jiaqing; Tang, Yiting; Chen, Weikang; Liu, Honglin

doi:10.1074/jbc.m112.349902

Cited by 158 publications

(167 citation statements)

References 80 publications

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“…15 Moreover, a previous study showed that ip injection of 3-NP elevated ovarian ROS levels in mice. 10 In ovarian GCs collected from 3-NP mice in the present study, a significant increase in caspase 3, Bim, and PUMA mRNA related to increased oxidative stress was found compared to controls (Figure 2A). These results confirm that 3-NP induces ovarian oxidative stress in mice and activates apoptotic pathways in follicular GCs.…”

Section: Administration Of 3-np Induced Gc Apoptosis and Upregulated supporting

confidence: 53%

Expression of PUMA in Follicular Granulosa Cells Regulated by FoxO1 Activation During Oxidative Stress

Liu

Shen

et al. 2015

Reprod. Sci.

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Many studies have demonstrated that oxidative stress-induced apoptosis is a main cause of follicular atresia. Reactive oxygen species (ROS)-induced granulosa cell (GC) apoptosis is regulated by a variety of signaling pathways involving numerous genes and transcription factors. In this study, we found expression of the p53-upregulated modulator of apoptosis (PUMA), a BH3-only Bcl-2 subfamily protein, in ovarian GCs during oxidative stress. By overexpression and knockdown of Forkhead box O1 (FoxO1), we found that FoxO1 regulates PUMA at the protein level. Moreover, as c-Jun N-terminal kinase (JNK) has been shown to activate FoxO1 by promoting its nuclear import, we used a JNK inhibitor to reduce FoxO1 activation and detected decreased PUMA messenger RNA expression and protein levels during oxidative stress. In addition, in vivo oxidative stress-induced upregulation of PUMA was found following injection of 3 nitropropionic acid in mice. In conclusion, oxidative stress increases PUMA expression regulated by FoxO1 in follicular GCs.

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Section: Administration Of 3-np Induced Gc Apoptosis and Upregulated supporting

confidence: 53%

Expression of PUMA in Follicular Granulosa Cells Regulated by FoxO1 Activation During Oxidative Stress

Liu

Shen

et al. 2015

Reprod. Sci.

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“…Animals were injected intraperitoneally with 12.5 mg/kg 3-NPA twice daily for 7 consecutive days at 12-h intervals (8 a.m. and 8 p.m.). The dose of 3-NPA used in the study was based on doses used in literature published from our laboratory (Shen et al, 2012). PC was dissolved in normal saline and supplemented to the animals by intragastric administration twice daily at a dose of 100 mg/kg body weight because this was reported to be the most effective dose (Bagchi et al, 1998a;Sato et al, 1999).…”

Section: Experimental Design and Treatmentmentioning

confidence: 99%

“…3-NPA, a natural toxin produced by various plants and fungi, is an inhibitor of succinate dehydrogenase and induces oxidative stress of mitochondrial origin (Fontaine et al, 2000;Kim et al, 2000). ROS levels that were specifically increased in follicular granulosa cells, but not other tissues, were detected following intraperitoneal injection of mice with 3-NPA (Shen et al, 2012). 3-NPA can significantly increase the production of lipid peroxides and oxidized protein levels both in the mitochondria and in the cytosol (Fu et al, 1995).…”

Section: Introductionmentioning

confidence: 98%

“…Several oxidants, including H 2 O 2 , nicotine, lead (Pb), methoxychlor, and 3-nitropropionic acid (3-NPA), cause oxidative stress and induce cell apoptosis (Taupeau et al, 2001;Yoon et al, 2002;Şener et al, 2005;Gupta et al, 2006). Among these, 3-NPA is the most effective for producing high ROS levels and triggering follicular granulosa apoptosis (Shen et al, 2012). 3-NPA, a natural toxin produced by various plants and fungi, is an inhibitor of succinate dehydrogenase and induces oxidative stress of mitochondrial origin (Fontaine et al, 2000;Kim et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Protective effect of proanthocyanidin against oxidative ovarian damage induced by 3-nitropropionic acid in mice

et al. 2015

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ABSTRACT.Oxidative stress, which poses a threat to reproductive health, causes many serious female reproductive diseases. In this study, we investigated whether proanthocyanidins (PC) have a protective effect against oxidative stress-induced ovarian damage. Forty female ICR mice were randomized into 4 groups: a control group, a control plus PC group, a 3-nitropropionic acid (3-NPA) group, and a 3-NPA plus PC group. An ovarian oxidative stress model induced by 3-NPA was constructed using female ICR mice. After the animals were sacrificed, their ovaries were collected to measure reactive oxygen species (ROS) levels, the activities of superoxide dismutase (SOD) and catalase (CAT), and the mRNA expression levels of relevant granulosa cell apoptosis genes Bax, Bim, FasL,. We also conducted a histological evaluation of granulosa cell apoptosis and follicular atresia. The results showed that compared to the 3-NPA group, ROS levels and activities of T-SOD and CAT in the 3-NPA plus PC group were significantly decreased (P < 0.05), while the ratio of Bcl-2 to Bax in the 3-NPA plus PC group were significantly increased (P < 0.05). mRNA expression levels of Bim, FasL, and caspase-3 in the 3-NPA plus PC group were significantly decreased (P < 0.05), and the percentage of atretic follicles and granulosa cell apoptosis in the 3-NPA plus PC group was significantly decreased (P < 0.05). Collectively, these data indicate that PC has significant protective effects against damage induced by oxidative stress in mouse ovaries. The mechanisms of protection may be related to antioxidation and apoptosis reduction.

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“…3 Previous studies have clearly demonstrated that granulosa cell (GC) apoptosis is the cellular mechanism responsible for follicular atresia in mammals 4 and that DNA fragmentation, caspase activation, up-regulation of pro-apoptotic and downregulation of anti-apoptotic gene expression are involved in this process. 5 In mammals, GC apoptosis is regulated by multiple factors such as reactive oxygen species (ROS), hormones, BCL2 family members and growth factors and cytokines, including tumor necrosis factor (TNF)-a and interleukin-6. 6 However, the precise molecular mechanism still needs to be further illuminated.…”

Section: Introductionmentioning

confidence: 99%

Age-associated up-regulation of EGR1 promotes granulosa cell apoptosis during follicle atresia in mice through the NF-κB pathway

et al. 2016

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Follicular atresia is the main process responsible for the loss of follicles and oocytes from the ovary, and it is the root cause of ovarian aging. Apoptosis of granulosa cells (GCs) is the cellular mechanism responsible for follicular atresia in mammals. Recent advances have highlighted fundamental roles for EGR1 in agerelated diseases via the induction of apoptosis. In the present study, we found that the expression of EGR1 was significantly increased in aged mouse ovaries compared with young ovaries. Immunohistochemical analysis revealed strongly positive EGR1 staining in atretic follicles, especially in apoptotic granulosa cells. We further showed that EGR1 up-regulation in mouse primary granulosa cells inhibited cell proliferation and promoted apoptosis. In addition, the promotion of apoptosis in GCs by EGR1 increases over time and with reactive oxygen species (ROS) stimulation. Our mechanistic study suggested that EGR1 regulates GC apoptosis in a mitochondria-dependent manner and that this mainly occurs through the NF-kB signaling pathway. In conclusion, our results suggested that age-related up-regulation of EGR1 promotes GC apoptosis in follicle atresia during ovarian aging.

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Involvement of the Up-regulated FoxO1 Expression in Follicular Granulosa Cell Apoptosis Induced by Oxidative Stress

Cited by 158 publications

References 80 publications

Expression of PUMA in Follicular Granulosa Cells Regulated by FoxO1 Activation During Oxidative Stress

Expression of PUMA in Follicular Granulosa Cells Regulated by FoxO1 Activation During Oxidative Stress

Protective effect of proanthocyanidin against oxidative ovarian damage induced by 3-nitropropionic acid in mice

Age-associated up-regulation of EGR1 promotes granulosa cell apoptosis during follicle atresia in mice through the NF-κB pathway

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